Keenan R J, Konishi H, Kawai A, Paradis I L, Nunley D R, Iacono A T, Hardesty R L, Weyant R J, Griffith B P
Division of Cardiothoracic Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
Ann Thorac Surg. 1995 Sep;60(3):580-4; discussion 584-5. doi: 10.1016/0003-4975(95)00407-C.
A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation.
Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease.
One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05).
This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.
开展了一项前瞻性临床试验，比较他克莫司（FK 506）与环孢素作为肺移植后主要免疫抑制剂的疗效。
在1991年10月至1994年5月期间，133名单肺和双肺移植受者被随机分配接受环孢素（n = 67）或他克莫司（n = 66）治疗。两组在年龄、性别和基础疾病方面相似。
两组的1年和2年生存率相似，尽管趋势是他克莫司组的生存率有所提高。他克莫司组每100患者日的急性排斥反应发作次数（0.85）少于环孢素组（1.09）（p = 0.07）。与环孢素组（38%）相比，他克莫司组发生闭塞性细支气管炎的患者明显较少（21.7%）（p = 0.025），并且接受他克莫司治疗的患者随着时间推移发生闭塞性细支气管炎的情况更少（p < 0.03）。需要从环孢素转换为他克莫司治疗的患者（n = 13）明显多于从他克莫司转换为环孢素治疗的患者（n = 2）（p = 0.02）。转换为他克莫司后，9例患者中有6例的持续性急性排斥反应得到控制。两组感染的总体发生率相似，尽管环孢素治疗时细菌感染更常见（p = 0.0375），而他克莫司治疗时真菌感染的风险更高（p < 0.05）。
该试验证明了他克莫司在降低闭塞性细支气管炎风险方面的优势，闭塞性细支气管炎是肺移植后长期发病和死亡的最重要原因。
